Autophagy pathways and functions in plant immunity and disease
Autophagy plays multifaceted roles in adaptive and innate immunity in animals, and is often manipulated or even hijacked by pathogens to increase infection. In plants, however, the mechanisms and functions of autophagy during pathogen infections remain poorly understood.
Previous work of the PI in association with the Mundy/Petersen lab (Copenhagen, Denmark) contributed to the discovery that autophagy promotes the hypersensitive response (HR) during effector-triggered immunity (Hofius et al. 2009, Cell) while preventing stress-associated “run-away” cell death outside of HR lesions (Munch et al., 2014, Autophagy). More recently, we showed that selective autophagy mediated by the autophagy cargo receptor NBR1 is integrated into basal immunity against viruses by targeting entire particles and/or individual viral proteins (Hafrén et al., 2017, PNAS; Hafren et al, 2018, Plant Physiol.). We further discovered that viruses have evolved measures to antagonize such antiviral “xenophagy”, and benefit from virus-induced “bulk” autophagy that prevents premature plant senescence and extends the timespan for virus production. In addition, we found that bacteria activate autophagy in an effector-dependent manner to degrade the proteasome (proteaphagy) for enhanced pathogenicity, whereas NBR1-dependent autophagy counteracts bacterial proliferation and disease-promoting “water-soaking” (Üstün et al., 2018, Plant Cell).
We currently investigate the mechanistic details of anti- and pro-microbial functions of autophagy. We follow different approaches to identify autophagic substrates during infection and search for host targets of pathogen effectors, which manipulate the autophagy pathway. Furthermore, we focus on dissecting the intimate crosstalk between autophagy and the ubiquitin-proteasome system during plant-pathogen interactions.
Related research articles and reviews
Kushwaha NK, Hafrén A, Hofius D (2019) Autophagy-virus interactions: from antiviral recognition to proviral manipulation. Mol. Plant Pathol 20, 1211-1216
Üstün, S., Hafren, A., Liu, Q., Marshall, R.S., Minina, E.A., Bozhkov, P., Vierstra, R.D., and Hofius, D. (2018). Bacteria exploit autophagy for proteasome degradation and enhanced virulence in plants. Plant Cell 30: 668–685
Hafren, A., Üstün, S., Hochmuth, A., Svenning, S., Johansen, T., and Hofius, D. (2018). Turnip Mosaic Virus Counteracts Selective Autophagy of the Viral Silencing Suppressor HCpro. Plant Physiol 176, 649-662.
Üstün, S., Hafren, A., and Hofius, D. (2017). Autophagy as a mediator of life and death in plants. Curr Opin Plant Biol 40, 122-130.
Hofius, D., Li, L., Hafren, A., and Coll, N.S. (2017). Autophagy as an emerging arena for plant-pathogen interactions. Curr Opin Plant Biol 38, 117-123.
Hafren, A., Macia, J.L., Love, A.J., Milner, J.J., Drucker, M., and Hofius, D. (2017). Selective autophagy limits cauliflower mosaic virus infection by NBR1-mediated targeting of viral capsid protein and particles. Proc Natl Acad Sci U S A 114, E2026-E2035.
Minina, E.A., Bozhkov, P.V., and Hofius, D. (2014). Autophagy as initiator or executioner of cell death. Trends Plant Sci 19, 692-697.
Munch, D., Rodriguez, E., Bressendorff, S., Park, O.K., Hofius, D., and Petersen, M. (2014). Autophagy deficiency leads to accumulation of ubiquitinated proteins, ER stress, and cell death in Arabidopsis. Autophagy 10, 1579-1587.
Hofius, D., Schultz-Larsen, T., Joensen, J., Tsitsigiannis, D.I., Petersen, N.H., Mattsson, O., Jorgensen, L.B., Jones, J.D., Mundy, J., and Petersen, M. (2009). Autophagic components contribute to hypersensitive cell death in Arabidopsis. Cell 137, 773-783.
Regulation of autophagy and pathogen-triggered cell death
Despite the recent advances in the understanding of autophagy and cell death processes in plants, their molecular regulation and cellular crosstalk during pathogen interactions remains to be largely resolved.
Mutant plants that display activated cell death and immune responses in the absence of pathogen attack (so-called lesion mimics) have been widely explored as genetic system to identify core components and regulatory networks of PCD and defence pathways. We have previously contributed to the characterisation of lazarus (laz) suppressors of the Arabidopsis lesion mimic mutant accelerated cell death11 (acd11). Cell death in acd11 is caused by the disruption of an sphingolipid (i.e., ceramide-1-phosphate) transfer protein and the subsequent activation of the immune receptor LAZ5. By analyzing the laz4/vps35b suppressor mutant, we provided evidence that membrane trafficking mediated by the conserved retromer complex contributes to immunity-related cell death and disease resistance. We further discovered a regulatory role of retromer components in the autophagic degradation pathway (Munch et al., 2015, Plant Cell). Another LAZ suppressor, LAZ1, and its closest homolog LAZ1H1 encode novel DUF300 domain-containing transmembrane proteins with tonoplast localization and similarity to steroid/organic solute transporters in animals. Our recent genetic and cell biological analysis revealed a role of these DUF300 proteins in maintaining vacuole integrity required for brassinosteroid signaling regulation (Liu et al, 2018, Mol. Plant).
We currently aim to further determine the molecular interplay of membrane trafficking and vacuole transport, as well as hormone and lipid signaling with autophagy and cell death processes. We are also interested in dissecting the epigenetic regulation of pathogen-triggered PCD and immune responses.
Dvořák Tomaštíková E, Hafrén A, Trejo-Arellano MS, Rasmussen SR, Santos-González J, Sako H, Köhler C, Hennig L, Hofius D (2021). Polycomb Repressive Complex 2 and KRYPTONITE regulate pathogen-induced programmed cell death in Arabidopsis. Plant Physiol. 185, 2003-2021 PubMed
Liu, Q., Vain, T., Viotti, C., Doyle, S.M., Tarkowska, D., Novak, O., Zipfel, C., Sitbon, F., Robert, S., and Hofius, D. (2018). Vacuole Integrity Maintained by DUF300 Proteins Is Required for Brassinosteroid Signaling Regulation. Mol Plant 11, 553-567.
Munch, D., Teh, O.K., Malinovsky, F.G., Liu, Q., Vetukuri, R.R., El Kasmi, F., Brodersen, P., Hara-Nishimura, I., Dangl, J.L., Petersen, M., Mundy, J., and Hofius, D. (2015). Retromer contributes to immunity-associated cell death in Arabidopsis. Plant Cell 27, 463-479.
Teh, O.K., and Hofius, D. (2014). Membrane trafficking and autophagy in pathogen-triggered cell death and immunity. J Exp Bot 65, 1297-1312.
Exploitation of autophagy for improved disease resistance and plant fitness
The emerging importance of autophagy in plant development, metabolism, stress adaptation, and immunity reveals its great potential as target for crop improvement. However, molecular strategies to modulate autophagy levels with beneficial effects on plant performance are largely lacking.
We have recently contributed to the finding that genetic stimulation of the autophagy activity improves resistance against necrotrophic fungi and oxidative stress tolerance in parallel with biomass production and seed yield in Arabidopsis (Minina et al. 2018).
Our long-term goal is to translate these strategies into crop species for improving disease and stress resistance, using e.g. CRISPR/Cas genome editing technologies.
Minina, E.A., Moschou, P.N., Vetukuri, R.R., Sanchez-Vera, V., Cardoso, C., Liu, Q., Elander, P.H., Dalman, K., Beganovic, M., Lindberg Yilmaz, J., Marmon, S., Shabala, L., Suarez, M.F., Ljung, K., Novak, O., Shabala, S., Stymne, S., Hofius, D., and Bozhkov, P.V. (2018). Transcriptional stimulation of rate-limiting components of the autophagic pathway improves plant fitness. J Exp Bot 69, 1415-1432.
Avin-Wittenberg, T., Baluska, F., Bozhkov, P.V., Elander, P.H., Fernie, A.R., Galili, G., Hassan, A., Hofius, D., Isono, E., Le Bars, R., Masclaux-Daubresse, C., Minina, E.A., Peled-Zehavi, H., Coll, N.S., Sandalio, L.M., Satiat-Jeunemaitre, B., Sirko, A., Testillano, P.S., and Batoko, H. (2018). Autophagy-related approaches for improving nutrient use efficiency and crop yield protection. J Exp Bot 69, 1335-1353.